International Journal of Psychiatry in Clinical Practice
ISSN: 1365-1501 (Print) 1471-1788 (Online) Journal homepage: http://www.tandfonline.com/loi/ijpc20
A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics Ifor Edwards, Emad Salib To cite this article: Ifor Edwards, Emad Salib (2001) A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics, International Journal of Psychiatry in Clinical Practice, 5:2, 129-134 To link to this article: http://dx.doi.org/10.1080/136515001300375172
Published online: 12 Jul 2009.
Submit your article to this journal
Article views: 2
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijpc20 Download by: [University of Birmingham]
Date: 06 November 2015, At: 02:24
Ó
2001 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2001 Volume 5 Pages 129 ± 134
129
A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics IFOR EDWARDS1 AND EMAD SALIB2 1
Warrington Community Health Care Trust and 2 Hollins Park Hospital, Warrington, UK
Available literature suggests that problems due to dependenc e do not result from the use of low doses of low-potency opioids used for short periods of time, but no studies looked at the effect of their long-term use. BACKGROUND:
The main objective of the study was to discover whether those patients on long-term low-potency opioids, and those on non-opioid analgesics, could suffer the problems of tolerance and dependence . The study also explored the validity of applying DCR-10 criteria to a nonproblemati c population of analgesic users in identifying drug-depend ent patients in primary care.
Downloaded by [University of Birmingham] at 02:24 06 November 2015
OBJECTIVES :
The prevalence of potential dependenc e amongst long-term users was assessed by a semi-structured questionnair e applying the DCR-10 criteria for Dependence Syndrome. The sample consisted of 38 randomly selected patients, drawn from four practices in North Cheshire, who had been on continuous repeat prescriptions of low-potency opioids, compound analgesics containing them and non-opioid analgesics (nonsteroidal anti-inflammatory drugs ± NSAIDs) for a minimum of one year, without any problems becoming apparent either to the patients or to their GPs. METHOD:
Correspondence Address Dr Ifor Edwards DRCOG MSc MRCGP, Senior Clinical Medical Officer, Hollins Park Hospital, Hollins Lane, Winwick, War rington WA2 8WA E-mail: [email protected]
Approximatel y 3.6% of the North Cheshire GP practice population , predominant ly elderly people, were shown to be on either opioid and/or non-opioid analgesics continuously for at least one year. An estimated 31% and 40% of patients on NSAIDs and low-potency opioids respectively fulfilled the DCR-10 criteria for Dependenc e Syndrome. With the exception of the criterion of `impaired control’ (odds ratio 4; P < 0.05), the DCR-10 criteria are equally likely to be reported in both groups. RESULTS:
An unexpectedl y high incidence of dependenc e was found, not only on opioids but also within the NSAIDs group. The findings may have resulted, at least in part, from an undetermined DCR-10 specificity. (Int J Psych Clin Pract 2001; 5: 129 ± 134) CONCLUSION:
Received 22 October 1998; revised 28 November 2000; accepted for publication 5 December 2000
Keywords long-term prescribing repeat prescriptions primary care compound analgesic s low-potency opioids non-steroida l anti-inflammatory drugs (NSAIDs)
INTRODUCTION
A
nalgesics are commonly prescribed in primary care. On prescription s for people of pensionable age, they
are second only in frequency to diuretics.1 In 1999, 42.7 million prescribed analgesi c items were dispensed from community pharmacies ± an increasing trend ± compared to 25.7 million for diuretics.2 Despite this, evaluation of
130
I Edwards and E Salib
their use is based on short-term use only, and little is known of the effects of long-term use.3 Mild to moderate pain in primary care is largely controlled by the use of low-potency opioids, such as codeine or dextropropoxyphene, and non-opioids , such as NSAID and paracetamol. Compound preparations are generally discourage d because of difficultie s in titrating the individua l components of pain.4 Nevertheless , the authors found that they were the most commonly prescribed group. Most recipient s were in the older age group, known to be more sensitive to adverse effects and drug interactions.
The study was conducted in North Cheshire, estimated population 350 000. Two group practices were selected from each of its two local authority districts, Warrington and Halton. Diagnostic Criteria for Research, 10t h revision (DCR-10) were used to identify possible substance dependence. The classificatio n is globally accepted as an instrument for medical research (Appendix 1).8
SAMPLE SELECTION (TABLE 1)
``A cluster of behavioural, cognitive and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state’’.5
Initially we selected all patients on repeat prescriptions , as recorded on computerized medical records; and of those, all patients who had been prescribed items listed in Sections 4.7.1 and 4.7.2 of the British National Formulary (BNF) were selected out. Those who had been receiving uninterrupted medication for a minimum of 12 months were identified, and their medical records were checked against those on computer to confirm continuous prescribing . Permissio n of the respective general practitioners (GPs) was sought formally before approaching the subjects themselves. The exclusion criteria were:
This psychiatric diagnosis is applied only to patients who have been referred to mental health services and who have what would more correctly be described as a problem of drug use or substance misuse that has caused concern to the individua l or their family ± ``addiction’’ in common parlance. Weissman and Haddox6 and Zenz et al7 claimed that repeated doses of low-potency opioids could induce tolerance in the same way as those of higher potency. The authors thus set out to explore the incidence of dependence, in primary care, in long-term recipients of low-potency opioids using DCR-10 criteria.8
severe physical infirmity or illness previousl y recognize d misuse of drugs or medication risk of provoking anxiety known current problems with pain control recent change of analgesic not yet recorded on computer records patients who had left the practice but who were still listed mental illness, especially confusiona l states or memory deficit individual s on both opioid(s) and NSAIDs.
DEPENDENCE SYNDROME This is defined in ICD-10 as: Downloaded by [University of Birmingham] at 02:24 06 November 2015
METHOD
Table 1 Summary of population and sampling District 1 practices GP 1 GP 2 n=19 458 n=10 545
Subjects All repeats Suitable Declined Unsuitable Failed contact Interviewed
Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID
279 58 12 5 5 1 0 0 3 1 4 3
101 59 10 6 2 2 1 1 2 3 4 1
District 2 Practices GP 3 GP 4 n=9987 n=13 606 387 173 10 9 2 0 1 1 1 2 6 5
380 186 20 10 4 1 2 1 0 3 13 5
Total
1147 476 52 30 13 4 4 3 6 9 27* 14*
131
Analgesic dependence
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DATA COLLECTION
Table 2 Proportions of opioid and NSAID scores on DCR-10 criteria
There are six manifestatio ns of the Substance Dependenc e Syndrome according to DCR-10 (Appendix 1).8 Each manifestation (criterion, for the purposes of this study) is characterize d by one or more features, such as a symptom, behaviour or consequence . The questionnair e was designed to reveal features that support the existence of a particular criterion. For example, the statement: ``I felt I had to take the painkiller s or I’d get very agitated’’ would be accepted as a feature of the sense of compulsion to take the specifie d drug. If the subject said: ``If I didn’t take the tablet, I wouldn’t sleep, even though I didn’t need it for the pain,’’ this would be interpreted as impaired capacity to control the use of that medication. One feature is sufficient to prove a criterion, but three criteria have to be present persistentl y or repeatedly to satisfy the definition of dependence. The criterion `withdrawal state’ is defined as either the withdrawal syndrome for that particular drug (there is none for NSAIDs) or the use of the same or similar drug with the intention of relieving or avoiding withdrawal symptoms. Three of the following constitute an opioid withdrawal state (DCR-10): craving lacrimation nausea or vomiting piloerectio n or chills yawning restless sleep
rhinorrhoe a or sneezing muscle aches/cramps pupil dilation tachycardia or hypertensio n abdominal cramps
Although each criterion was dealt with in a similar fashion, Criterion 5 (see Appendix 1) was thought to be irrelevant to this population (and potentially upsetting!).
STATISTICAL ANALYSIS (TABLE 2) The sample was small and the distribution of dependence criteria and their features were not known for the general population or for the study population. Non-paramet ric statistical tests to compare means and proportions were therefore thought to be appropriat e for analysis. The Pvalues are for Fisher exact tests used when the number of cell values in the 2 ´ 2 tables is less than five. Significanc e levels were decided at the 5% level using Pearson’ s x 2 for the categorical variables and the Mann-Whitney U-test for interval variables. Univariat e odds ratios were calculated using 2 ´ 2 tables as follows: ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ DCR-10 criterion Opioid group NSAID group ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Present a b Absent c d ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Odds ratio (OR)=(a ´ d)/(c ´ d)
DCR-10 criterion 1. Compulsion eg, urgent need 2. Impaired control eg, craving more than advised longer than intended failed attempts to reduce desire to reduce/stop 3. Abstinence symptoms eg, physiological withdrawal irritability restlessness bad-tempered mood low anxiety substitute for withdrawal 4. Tolerance eg, diminished effect increased dose 5. Persistent use eg, use despite side-effects use despite danger a
Opioid group n=25
NSAID group n=13
8 (32%) 16 (64%)
2 (15%) 4 (30%)
12 (48%)
4 (30%)
1.01 0.3
14 (56%)
6 (46%)
0.32 0.6
8 (32%)
5 0.15a 0.7b (38%)
v
2
P
0.9a 0.2b 3.79 0.05
Yates corrected One-tailed Fisher exact
b
An odds ratio of 1 indicates no association, whereas an OR < 1 means a negative association, and an OR > 1 a positive association. ORs are presented with a confidence interval (CI) of 95%, and a x 2 test of significanc e at the 5% level. EPI-Info, 6t h version was used for data entry and statistical analysis.9
RESULTS From a total GP patient population of 43 588, the sample included 41 patients from four practices who had been on repeat prescriptio ns for oral analgesic s for 1 year or more without apparent problems. For exclusion criteria, see Method section, above. Thirty-eigh t questionnair es (12 male and 26 female) were completed satisfactorily .
PROFILE OF SAMPLE GROUPS The opioid group numbered 25 (65.8%); 13 (34.2%) were on NSAIDs. Age and gender The mean age was 64 years (SD 11: 48 ± 87 years). There was no significan t difference in mean age between the
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I Edwards and E Salib
opioid and NSAID groups (67 and 62 years respectively) , but women patients on opioids were older (mean ages: men 56, women 69 years). There were significantl y more women on opioids than on NSAIDs (76% vs. 24%: P < 0.05), whereas for men the figures were 54% and 46%.
Downloaded by [University of Birmingham] at 02:24 06 November 2015
Prescribe d items Opioids Dextropropoxyphene/paracetamol Codeine 8 mg/paracetamol Codeine 30 mg/paracetamol Dihydrocodei ne 10 mg/paracetamol Dihydrocodei ne 30 mg/paracetamol Tramadol NSAID +/- paracetamol
No. of cases 16 (64%) 4 (16%) 1 (4%) 2 ( 8%) 1 (4%) 1 (4%) 13
sample). No subjects taking dihydrocode ine scored as dependent (Table 3). Thus 14 (36.8%) were substance-de pendent. Of these, 10 were on opioids and four on NSAIDs; hence NSAID patients accounted for 10.5% of the total sample that fulfilled the criteria for dependence, and opioid users accounted for 26.3%. Table 4 shows the odds ratios (ORs) for each criterion, comparing the two groups. The values of ORs and confidence intervals appear to suggest that impaired control was the only criterion which achieved statistical significanc e at 5% probability between the two groups. The DCR-10 criteria for substance dependence, with the exception of impaired control, appear to be equally likely to have been reported in both groups.
ICD-10 SCORE (TABLES 3 & 4)
DISCUSSION
Seven patients on dextropropoxyphene fulfilled the criteria for dependence, representing 18% of the total sample. Of those taking codeine, three were dependent ± 8% of the total. Four NSAID patients fulfille d the required minimum of three criteria for substance dependence (31% of the total
METHODOLOGICAL ISSUES This paper should be seen as a pilot study in view of the small size of the sample, which increases the probabilit y of a Type II error.
Table 3 Scores for DCR-10: criteria and features Criteria scores NSAID=21 Mean=1.6
Criteria scores Opioid=58 Mean=2.3
Feature scores NSAID=35 Mean=3
Feature scores Opioid=82 Mean=3.3
1. Compulsion urgent need 2. Impaired control of use craving more than advised/intended longer than intended failed attempts to reduce desire to reduce/stop
2 (10%)
8 (14%)
2 (6%)
8 (10%)
4 (19%)
16 (28%)**
3. Abstinence symptoms physiological withdrawals irritability restlessness bad-tempered mood low other (ie anxiety) substitute for withdrawals
4 (19%)
4. Evidence of tolerance diminished effect increased dose
6 (28%)
5. Persistent use use despite side-effects use despite danger
5 (24%)
Criteria and features
**P0.05a
One-tailed Fisher exact
The specificity of the criteria within ICD-10 has not been determined. This allows for greater interpretive variation. The authors were aware from the outset that scoring diagnostic criteria may magnify this weakness. Nevertheless , they are conversant with the WHO Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders,5 and feel that the questionnair e served well as a method of taking a relevant formal and detailed history. Observer bias may have affected the findings, as may selection (e.g., the selection of interviewees by their own family doctors) and information bias.
INTERPRETATION OF FINDINGS This was a preliminar y study, and extensive literature searches failed to reveal any results of studies of long-term low-potency opioid medication for comparison. The findings suggest that 459 out of 43 588 primary care patients are substance-de pendent. The high incidence, though statistically plausible , requires critical examination. It is noted that the ICD-10 definition of substance
133
dependence (see above),5 is mainly applicabl e to psychiatric referrals , for whom a more appropriat e description may be `problematic drug use’. It is universall y accepted that physiologic al tolerance to opioids develops with long-term frequent use. Although we found that overall control of pain was incomplete, this was not reflected in patients taking doses larger than those recommended in the BNF. The maximum daily dose of compound analgesics advised in the BNF was based on the paracetamol content (because of potential hepatotoxicity), not the opioid content. The authors observed that pain control was often inadequate because of dosage constraints. We could not find evidence that the sensitivit y to the sideeffects of opioids increase d with age. Finally, the authors became increasingl y aware that the DCR-10 definition of dependence, applied mechanistical ly to the sample, may lack validity. Reliabilit y was of less concern, as both the NSAID and the opioid group were found to have a high incidence of dependence.
CONCLUSION There is a strong suggestion that impaired control of intake of dosage of opioids occurs more frequently than that of non-opioids , when used long-term. This finding, and others, depend almost entirely on the validity of the DCR-10 definition of substance dependence, and its specificit y as an instrument. The high incidenc e of substance dependence in this population, as indicated by this pilot study, gives rise to concern about the value of DCR-10 in its diagnosis. The fear of dependence may result in the undertreatment of pain.
KEY POINTS
· · ·
THis is the first exploration into long-term use of low-potency opioids in primary care Applying DCR-10 criteria returns a high incidence of dependence The equally unexpected high incidence in longterm non-opioi d recipients raises questions about the validity of DCR-10 as a diagnostic instrument in this population
REFERENCES 1. Anon (1990) Elderly people, their medicines and their doctors. Drugs Therapeutics Bull 28: 77 ± 79. 2. Department of Health Statistical Bulletin, August 2000. Stationery Office, London. 3. National Prescribing Center, Liverpool. The use of oral analgesics in Primary Care II (1) May MeRec Bulletin.
4. British National Formulary (September 2000). The Pharmaceutical Press, Wallingford. 40: 204. 5. World Health Organization (1992) The International Classification of Diseases, 10th revision (ICD-10). Mental and Behavioural Disorders. WHO, Geneva.
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6. Weissman DE, Haddox JD (1989) Opioid pseudoaddiction ± an iatrogenic syndrome. Pain 36: 363 ± 6. 7. Zenz M, Strumpf M, Tryba M (February 1992) Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 7(2): 69 ± 77
Appendix 1
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The Dependence Syndrome (DCR-10)8 Three or more of the following manifestation s would have occurred together for at least 1 month or, if persisting for periods of less than 1 month, would have occurred together repeatedly within a 12-month period: 1. A strong sense of compulsion to take the substance. 2. Impaired capacity to control substance-usi ng behaviour in terms of its onset, termination, or level of use, as evidence by substance being used often in larger amounts or over a longer period than intended, or by a persistent desire or unsuccessfu l efforts to reduce or control substance use. 3. A physiologic al withdrawal state when substance used is reduced or ceased, as evidenced by the character-
8. WHO (1993) The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Ch. 5. Geneva. World Medical Organisation. 9. Epi-Info Version 6.02 (October 1994). USD Inc, 2075-A West Park Place, Stone Mountain, CA 30087, USA.
istic withdrawal syndrome for that substance, or by the use of the same (or closely related) substance with the intention of relieving or avoiding withdrawal symptom. 4. Evidence of tolerance to the effects of the substance , such that there is a need for significantl y increased amounts of the substance to achieve intoxication or the desired effect or a markedly diminishe d effect with the continued use of the same amount of the substance. 5. Preoccupation with substance use, as manifested by important alternative pleasures or interests being given up or reduced because of substance use; or a great deal of time being spent in activities necessary to obtain, take or recover from the effects of the substance. 6. Persistent substance use despite clear evidence of harmful consequence s, as evidenced by continued use when the individual is actually aware, or may be expected to be aware, of the nature and extent of harm.
ISSN: 1365-1501 (Print) 1471-1788 (Online) Journal homepage: http://www.tandfonline.com/loi/ijpc20
A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics Ifor Edwards, Emad Salib To cite this article: Ifor Edwards, Emad Salib (2001) A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics, International Journal of Psychiatry in Clinical Practice, 5:2, 129-134 To link to this article: http://dx.doi.org/10.1080/136515001300375172
Published online: 12 Jul 2009.
Submit your article to this journal
Article views: 2
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijpc20 Download by: [University of Birmingham]
Date: 06 November 2015, At: 02:24
Ó
2001 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2001 Volume 5 Pages 129 ± 134
129
A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics IFOR EDWARDS1 AND EMAD SALIB2 1
Warrington Community Health Care Trust and 2 Hollins Park Hospital, Warrington, UK
Available literature suggests that problems due to dependenc e do not result from the use of low doses of low-potency opioids used for short periods of time, but no studies looked at the effect of their long-term use. BACKGROUND:
The main objective of the study was to discover whether those patients on long-term low-potency opioids, and those on non-opioid analgesics, could suffer the problems of tolerance and dependence . The study also explored the validity of applying DCR-10 criteria to a nonproblemati c population of analgesic users in identifying drug-depend ent patients in primary care.
Downloaded by [University of Birmingham] at 02:24 06 November 2015
OBJECTIVES :
The prevalence of potential dependenc e amongst long-term users was assessed by a semi-structured questionnair e applying the DCR-10 criteria for Dependence Syndrome. The sample consisted of 38 randomly selected patients, drawn from four practices in North Cheshire, who had been on continuous repeat prescriptions of low-potency opioids, compound analgesics containing them and non-opioid analgesics (nonsteroidal anti-inflammatory drugs ± NSAIDs) for a minimum of one year, without any problems becoming apparent either to the patients or to their GPs. METHOD:
Correspondence Address Dr Ifor Edwards DRCOG MSc MRCGP, Senior Clinical Medical Officer, Hollins Park Hospital, Hollins Lane, Winwick, War rington WA2 8WA E-mail: [email protected]
Approximatel y 3.6% of the North Cheshire GP practice population , predominant ly elderly people, were shown to be on either opioid and/or non-opioid analgesics continuously for at least one year. An estimated 31% and 40% of patients on NSAIDs and low-potency opioids respectively fulfilled the DCR-10 criteria for Dependenc e Syndrome. With the exception of the criterion of `impaired control’ (odds ratio 4; P < 0.05), the DCR-10 criteria are equally likely to be reported in both groups. RESULTS:
An unexpectedl y high incidence of dependenc e was found, not only on opioids but also within the NSAIDs group. The findings may have resulted, at least in part, from an undetermined DCR-10 specificity. (Int J Psych Clin Pract 2001; 5: 129 ± 134) CONCLUSION:
Received 22 October 1998; revised 28 November 2000; accepted for publication 5 December 2000
Keywords long-term prescribing repeat prescriptions primary care compound analgesic s low-potency opioids non-steroida l anti-inflammatory drugs (NSAIDs)
INTRODUCTION
A
nalgesics are commonly prescribed in primary care. On prescription s for people of pensionable age, they
are second only in frequency to diuretics.1 In 1999, 42.7 million prescribed analgesi c items were dispensed from community pharmacies ± an increasing trend ± compared to 25.7 million for diuretics.2 Despite this, evaluation of
130
I Edwards and E Salib
their use is based on short-term use only, and little is known of the effects of long-term use.3 Mild to moderate pain in primary care is largely controlled by the use of low-potency opioids, such as codeine or dextropropoxyphene, and non-opioids , such as NSAID and paracetamol. Compound preparations are generally discourage d because of difficultie s in titrating the individua l components of pain.4 Nevertheless , the authors found that they were the most commonly prescribed group. Most recipient s were in the older age group, known to be more sensitive to adverse effects and drug interactions.
The study was conducted in North Cheshire, estimated population 350 000. Two group practices were selected from each of its two local authority districts, Warrington and Halton. Diagnostic Criteria for Research, 10t h revision (DCR-10) were used to identify possible substance dependence. The classificatio n is globally accepted as an instrument for medical research (Appendix 1).8
SAMPLE SELECTION (TABLE 1)
``A cluster of behavioural, cognitive and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state’’.5
Initially we selected all patients on repeat prescriptions , as recorded on computerized medical records; and of those, all patients who had been prescribed items listed in Sections 4.7.1 and 4.7.2 of the British National Formulary (BNF) were selected out. Those who had been receiving uninterrupted medication for a minimum of 12 months were identified, and their medical records were checked against those on computer to confirm continuous prescribing . Permissio n of the respective general practitioners (GPs) was sought formally before approaching the subjects themselves. The exclusion criteria were:
This psychiatric diagnosis is applied only to patients who have been referred to mental health services and who have what would more correctly be described as a problem of drug use or substance misuse that has caused concern to the individua l or their family ± ``addiction’’ in common parlance. Weissman and Haddox6 and Zenz et al7 claimed that repeated doses of low-potency opioids could induce tolerance in the same way as those of higher potency. The authors thus set out to explore the incidence of dependence, in primary care, in long-term recipients of low-potency opioids using DCR-10 criteria.8
severe physical infirmity or illness previousl y recognize d misuse of drugs or medication risk of provoking anxiety known current problems with pain control recent change of analgesic not yet recorded on computer records patients who had left the practice but who were still listed mental illness, especially confusiona l states or memory deficit individual s on both opioid(s) and NSAIDs.
DEPENDENCE SYNDROME This is defined in ICD-10 as: Downloaded by [University of Birmingham] at 02:24 06 November 2015
METHOD
Table 1 Summary of population and sampling District 1 practices GP 1 GP 2 n=19 458 n=10 545
Subjects All repeats Suitable Declined Unsuitable Failed contact Interviewed
Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID Opioid NSAID
279 58 12 5 5 1 0 0 3 1 4 3
101 59 10 6 2 2 1 1 2 3 4 1
District 2 Practices GP 3 GP 4 n=9987 n=13 606 387 173 10 9 2 0 1 1 1 2 6 5
380 186 20 10 4 1 2 1 0 3 13 5
Total
1147 476 52 30 13 4 4 3 6 9 27* 14*
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DATA COLLECTION
Table 2 Proportions of opioid and NSAID scores on DCR-10 criteria
There are six manifestatio ns of the Substance Dependenc e Syndrome according to DCR-10 (Appendix 1).8 Each manifestation (criterion, for the purposes of this study) is characterize d by one or more features, such as a symptom, behaviour or consequence . The questionnair e was designed to reveal features that support the existence of a particular criterion. For example, the statement: ``I felt I had to take the painkiller s or I’d get very agitated’’ would be accepted as a feature of the sense of compulsion to take the specifie d drug. If the subject said: ``If I didn’t take the tablet, I wouldn’t sleep, even though I didn’t need it for the pain,’’ this would be interpreted as impaired capacity to control the use of that medication. One feature is sufficient to prove a criterion, but three criteria have to be present persistentl y or repeatedly to satisfy the definition of dependence. The criterion `withdrawal state’ is defined as either the withdrawal syndrome for that particular drug (there is none for NSAIDs) or the use of the same or similar drug with the intention of relieving or avoiding withdrawal symptoms. Three of the following constitute an opioid withdrawal state (DCR-10): craving lacrimation nausea or vomiting piloerectio n or chills yawning restless sleep
rhinorrhoe a or sneezing muscle aches/cramps pupil dilation tachycardia or hypertensio n abdominal cramps
Although each criterion was dealt with in a similar fashion, Criterion 5 (see Appendix 1) was thought to be irrelevant to this population (and potentially upsetting!).
STATISTICAL ANALYSIS (TABLE 2) The sample was small and the distribution of dependence criteria and their features were not known for the general population or for the study population. Non-paramet ric statistical tests to compare means and proportions were therefore thought to be appropriat e for analysis. The Pvalues are for Fisher exact tests used when the number of cell values in the 2 ´ 2 tables is less than five. Significanc e levels were decided at the 5% level using Pearson’ s x 2 for the categorical variables and the Mann-Whitney U-test for interval variables. Univariat e odds ratios were calculated using 2 ´ 2 tables as follows: ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ DCR-10 criterion Opioid group NSAID group ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Present a b Absent c d ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Odds ratio (OR)=(a ´ d)/(c ´ d)
DCR-10 criterion 1. Compulsion eg, urgent need 2. Impaired control eg, craving more than advised longer than intended failed attempts to reduce desire to reduce/stop 3. Abstinence symptoms eg, physiological withdrawal irritability restlessness bad-tempered mood low anxiety substitute for withdrawal 4. Tolerance eg, diminished effect increased dose 5. Persistent use eg, use despite side-effects use despite danger a
Opioid group n=25
NSAID group n=13
8 (32%) 16 (64%)
2 (15%) 4 (30%)
12 (48%)
4 (30%)
1.01 0.3
14 (56%)
6 (46%)
0.32 0.6
8 (32%)
5 0.15a 0.7b (38%)
v
2
P
0.9a 0.2b 3.79 0.05
Yates corrected One-tailed Fisher exact
b
An odds ratio of 1 indicates no association, whereas an OR < 1 means a negative association, and an OR > 1 a positive association. ORs are presented with a confidence interval (CI) of 95%, and a x 2 test of significanc e at the 5% level. EPI-Info, 6t h version was used for data entry and statistical analysis.9
RESULTS From a total GP patient population of 43 588, the sample included 41 patients from four practices who had been on repeat prescriptio ns for oral analgesic s for 1 year or more without apparent problems. For exclusion criteria, see Method section, above. Thirty-eigh t questionnair es (12 male and 26 female) were completed satisfactorily .
PROFILE OF SAMPLE GROUPS The opioid group numbered 25 (65.8%); 13 (34.2%) were on NSAIDs. Age and gender The mean age was 64 years (SD 11: 48 ± 87 years). There was no significan t difference in mean age between the
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I Edwards and E Salib
opioid and NSAID groups (67 and 62 years respectively) , but women patients on opioids were older (mean ages: men 56, women 69 years). There were significantl y more women on opioids than on NSAIDs (76% vs. 24%: P < 0.05), whereas for men the figures were 54% and 46%.
Downloaded by [University of Birmingham] at 02:24 06 November 2015
Prescribe d items Opioids Dextropropoxyphene/paracetamol Codeine 8 mg/paracetamol Codeine 30 mg/paracetamol Dihydrocodei ne 10 mg/paracetamol Dihydrocodei ne 30 mg/paracetamol Tramadol NSAID +/- paracetamol
No. of cases 16 (64%) 4 (16%) 1 (4%) 2 ( 8%) 1 (4%) 1 (4%) 13
sample). No subjects taking dihydrocode ine scored as dependent (Table 3). Thus 14 (36.8%) were substance-de pendent. Of these, 10 were on opioids and four on NSAIDs; hence NSAID patients accounted for 10.5% of the total sample that fulfilled the criteria for dependence, and opioid users accounted for 26.3%. Table 4 shows the odds ratios (ORs) for each criterion, comparing the two groups. The values of ORs and confidence intervals appear to suggest that impaired control was the only criterion which achieved statistical significanc e at 5% probability between the two groups. The DCR-10 criteria for substance dependence, with the exception of impaired control, appear to be equally likely to have been reported in both groups.
ICD-10 SCORE (TABLES 3 & 4)
DISCUSSION
Seven patients on dextropropoxyphene fulfilled the criteria for dependence, representing 18% of the total sample. Of those taking codeine, three were dependent ± 8% of the total. Four NSAID patients fulfille d the required minimum of three criteria for substance dependence (31% of the total
METHODOLOGICAL ISSUES This paper should be seen as a pilot study in view of the small size of the sample, which increases the probabilit y of a Type II error.
Table 3 Scores for DCR-10: criteria and features Criteria scores NSAID=21 Mean=1.6
Criteria scores Opioid=58 Mean=2.3
Feature scores NSAID=35 Mean=3
Feature scores Opioid=82 Mean=3.3
1. Compulsion urgent need 2. Impaired control of use craving more than advised/intended longer than intended failed attempts to reduce desire to reduce/stop
2 (10%)
8 (14%)
2 (6%)
8 (10%)
4 (19%)
16 (28%)**
3. Abstinence symptoms physiological withdrawals irritability restlessness bad-tempered mood low other (ie anxiety) substitute for withdrawals
4 (19%)
4. Evidence of tolerance diminished effect increased dose
6 (28%)
5. Persistent use use despite side-effects use despite danger
5 (24%)
Criteria and features
**P0.05a
One-tailed Fisher exact
The specificity of the criteria within ICD-10 has not been determined. This allows for greater interpretive variation. The authors were aware from the outset that scoring diagnostic criteria may magnify this weakness. Nevertheless , they are conversant with the WHO Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders,5 and feel that the questionnair e served well as a method of taking a relevant formal and detailed history. Observer bias may have affected the findings, as may selection (e.g., the selection of interviewees by their own family doctors) and information bias.
INTERPRETATION OF FINDINGS This was a preliminar y study, and extensive literature searches failed to reveal any results of studies of long-term low-potency opioid medication for comparison. The findings suggest that 459 out of 43 588 primary care patients are substance-de pendent. The high incidence, though statistically plausible , requires critical examination. It is noted that the ICD-10 definition of substance
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dependence (see above),5 is mainly applicabl e to psychiatric referrals , for whom a more appropriat e description may be `problematic drug use’. It is universall y accepted that physiologic al tolerance to opioids develops with long-term frequent use. Although we found that overall control of pain was incomplete, this was not reflected in patients taking doses larger than those recommended in the BNF. The maximum daily dose of compound analgesics advised in the BNF was based on the paracetamol content (because of potential hepatotoxicity), not the opioid content. The authors observed that pain control was often inadequate because of dosage constraints. We could not find evidence that the sensitivit y to the sideeffects of opioids increase d with age. Finally, the authors became increasingl y aware that the DCR-10 definition of dependence, applied mechanistical ly to the sample, may lack validity. Reliabilit y was of less concern, as both the NSAID and the opioid group were found to have a high incidence of dependence.
CONCLUSION There is a strong suggestion that impaired control of intake of dosage of opioids occurs more frequently than that of non-opioids , when used long-term. This finding, and others, depend almost entirely on the validity of the DCR-10 definition of substance dependence, and its specificit y as an instrument. The high incidenc e of substance dependence in this population, as indicated by this pilot study, gives rise to concern about the value of DCR-10 in its diagnosis. The fear of dependence may result in the undertreatment of pain.
KEY POINTS
· · ·
THis is the first exploration into long-term use of low-potency opioids in primary care Applying DCR-10 criteria returns a high incidence of dependence The equally unexpected high incidence in longterm non-opioi d recipients raises questions about the validity of DCR-10 as a diagnostic instrument in this population
REFERENCES 1. Anon (1990) Elderly people, their medicines and their doctors. Drugs Therapeutics Bull 28: 77 ± 79. 2. Department of Health Statistical Bulletin, August 2000. Stationery Office, London. 3. National Prescribing Center, Liverpool. The use of oral analgesics in Primary Care II (1) May MeRec Bulletin.
4. British National Formulary (September 2000). The Pharmaceutical Press, Wallingford. 40: 204. 5. World Health Organization (1992) The International Classification of Diseases, 10th revision (ICD-10). Mental and Behavioural Disorders. WHO, Geneva.
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6. Weissman DE, Haddox JD (1989) Opioid pseudoaddiction ± an iatrogenic syndrome. Pain 36: 363 ± 6. 7. Zenz M, Strumpf M, Tryba M (February 1992) Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 7(2): 69 ± 77
Appendix 1
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The Dependence Syndrome (DCR-10)8 Three or more of the following manifestation s would have occurred together for at least 1 month or, if persisting for periods of less than 1 month, would have occurred together repeatedly within a 12-month period: 1. A strong sense of compulsion to take the substance. 2. Impaired capacity to control substance-usi ng behaviour in terms of its onset, termination, or level of use, as evidence by substance being used often in larger amounts or over a longer period than intended, or by a persistent desire or unsuccessfu l efforts to reduce or control substance use. 3. A physiologic al withdrawal state when substance used is reduced or ceased, as evidenced by the character-
8. WHO (1993) The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Ch. 5. Geneva. World Medical Organisation. 9. Epi-Info Version 6.02 (October 1994). USD Inc, 2075-A West Park Place, Stone Mountain, CA 30087, USA.
istic withdrawal syndrome for that substance, or by the use of the same (or closely related) substance with the intention of relieving or avoiding withdrawal symptom. 4. Evidence of tolerance to the effects of the substance , such that there is a need for significantl y increased amounts of the substance to achieve intoxication or the desired effect or a markedly diminishe d effect with the continued use of the same amount of the substance. 5. Preoccupation with substance use, as manifested by important alternative pleasures or interests being given up or reduced because of substance use; or a great deal of time being spent in activities necessary to obtain, take or recover from the effects of the substance. 6. Persistent substance use despite clear evidence of harmful consequence s, as evidenced by continued use when the individual is actually aware, or may be expected to be aware, of the nature and extent of harm.
